Trypanosoma brucei ribonuclease H2A is an essential enzyme that resolves R-loops associated with transcription initiation and antigenic variation
Trypanosoma brucei ribonuclease H2A is an essential enzyme that resolves R-loops associated with transcription initiation and antigenic variation
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布氏锥虫核糖核酸酶 H2A 是一种必需酶，可解析与转录起始和抗原变异相关的 R 环
DOI：
10.1101/541300
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Briggs E
中科院分区：
文献类型：
--
作者：
Briggs E
在每个细胞中，核糖核苷酸都对DNA基因组的稳定性和传递构成威胁。两种类型的核糖核酸酶H（RNase H）处理这样的核糖核苷酸，当它们形成DNA链的一部分时通过切除，或者当RNA与DNA碱基配对时通过水解RNA，在称为R环的结构中。在哺乳动物中，任何一种核糖核酸酶H的缺失都是致命的，而酵母在两种酶都缺失的情况下也能繁荣。去除RNase H1是耐受的寄生虫布氏锥虫，但没有工作已经检查RNase H2的功能。在这里，我们表明，T的催化亚基的损失。布鲁氏菌RNA酶H2（TbRH 2A）导致生长和细胞周期停滞，这伴随着在RNA聚合酶（Pol）II转录起始位点处的核损伤的积累，揭示了RNA酶H2的新颖且关键的作用。此外，RNA Pol I和II转录基因的差异基因表达发生在TbRH 2A丢失后，包括可能与患有自身免疫性疾病的人中的细胞溶质DNA积累相关的模式。最后，我们表明，TbRH 2A的损失导致R-环和DNA损伤的端粒RNA聚合酶I转录位点的积累，导致改变的变体表面糖蛋白的表达。因此，我们证明了两个核T之间的功能分离。在RNA Pol II转录过程中，布鲁氏菌RNA酶H酶的功能是重叠的，但在宿主免疫逃避过程中，RNA Pol I介导的基因表达过程中，功能是重叠的。
In every cell ribonucleotides represent a threat to the stability and transmission of the DNA genome. Two types of Ribonuclease H (RNase H) tackle such ribonucleotides, either by excision when they form part of the DNA strand, or by hydrolysing RNA when it base-pairs with DNA, in structures termed R-loops. Loss of either RNase H is lethal in mammals, whereas yeast can prosper in the absence of both enzymes. Removal of RNase H1 is tolerated by the parasiteTrypanosoma bruceibut no work has examined the function of RNase H2. Here we show that loss of the catalytic subunit ofT. bruceiRNase H2 (TbRH2A) leads to growth and cell cycle arrest that is concomitant with accumulation of nuclear damage at sites of RNA polymerase (Pol) II transcription initiation, revealing a novel and critical role for RNase H2. In addition, differential gene expression of both RNA Pol I and II transcribed genes occurs after TbRH2A loss, including patterns that may relate to cytosolic DNA accumulation in humans with autoimmune disease. Finally, we show that TbRH2A loss causes R-loop and DNA damage accumulation in telomeric RNA Pol I transcription sites, leading to altered variant surface glycoprotein expression. Thus, we demonstrate a separation of function between the two nuclearT. bruceiRNase H enzymes during RNA Pol II transcription, but overlap in function during RNA Pol I-mediated gene expression during host immune evasion.
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影响因子：
16
作者：
Wahba, Lamia;Amon, Jeremy D.;Koshland, Douglas;Vuica-Ross, Milena
通讯作者：
Vuica-Ross, Milena
影响因子：
16
作者：
Sparks, Justin L.;Chon, Hyongi;Cerritelli, Susana M.;Kunkel, Thomas A.;Johansson, Erik;Crouch, Robert J.;Burgers, Peter M.
通讯作者：
Burgers, Peter M.
DOI：
10.1073/pnas.1600344113
发表时间：
2016-06-28
影响因子：
11.1
作者：
Glover, Lucy;Hutchinson, Sebastian;Horn, David
通讯作者：
Horn, David
转录复制冲突取向调节R环水平并激活不同的DNA损伤反应。
影响因子：
64.5
作者：
Hamperl S;Bocek MJ;Saldivar JC;Swigut T;Cimprich KA
通讯作者：
Cimprich KA
影响因子：
16.6
作者：
Burgers PMJ;Kunkel TA
通讯作者：
Kunkel TA